The Effect of Cilostazol on Electrocardiographic Parameters in Patients with Peripheral Artery Disease Initiating Cilostazol Treatment

Yıl 2023, Cilt: 26 Sayı: 2, 70 - 75, 12.07.2023

Muhammed Bahadır Omar Kenan Toprak Khagani Isgandarov Münevver Sarı Elnur Alizade Selçuk Pala

Öz

Introduction: One of the pharmacological treatment options for improving the symptoms of peripheral artery disease (PAD) and increasing the quality of life is cilostazol. Cilostazol is a pharmacological agent that shows vasodilator activity mainly by reducing cAMP degradation through specific cellular phosphodiesterase 3A enzyme inhibition. The effect of cilostazol on electrocardiographic parameters is not clear. In this study, we aimed to examine the effect of cilostazol on electrocardiographic parameters in PAD patients.

Patients and Methods: The study included a total of 32 patients diagnosed with intermittent claudication and peripheral artery disease (PAD), who were selected for medical treatment based on peripheral artery imaging. The subjects were started on 100 mg of cilostazol twice a day. The electrocardiographic measurements of the subjects before the cilostazol treatment and three months after the initiation of cilostazol were compared.

Results: After a period of three months, statistically significant prolongation was observed in the ventricular repolarization parameters QTd, QTc, and Tpe of the subjects compared to their premedication values (p= 0.01, for all).

Conclusion: It is known that patients with peripheral artery disease (PAD) are at an increased risk of major adverse cardiovascular events (MACE), including sudden cardiac death (SCD). In this context, close monitoring of electrocardiography markers for ventricular repolarization heterogeneity, such as QTd, QTc, and Tpe, is necessary when initiating cilostazol therapy in patients with peripheral artery disease (PAD). These markers may be closely associated with major adverse cardiovascular events (MACE), including sudden cardiac death (SCD), and therefore require careful monitoring in PAD patients receiving cilostazol treatment.

Anahtar Kelimeler

Cilostazol, electrocardiographic parameters, peripheral artery disease

Kaynakça

• 1. Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss LK, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society for Vascular Medicine; Society for Vascular Surgery. 2011 ACCF/ AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine, and Society for Vascular Surgery. J Vasc Surg 2011;54(5):32-58. [Crossref]
• 2. Hamburg NM, Creager MA. Pathophysiology of intermittent claudication in peripheral artery disease. Circ J 2017;81(3):281-9. [Crossref]
• 3. Firnhaber JM, Powell CS. Lower extremity peripheral artery disease: Diagnosis and treatment. Am Fam Physician 2019;99(6):362-9. Am Fam Physician 2019;100(2):74.
• 4. Beebe HG, Dawson DL, Cutler BS, Herd JA, Strandness DE Jr, Bortey EB, et al. A new pharmacological treatment for intermittent claudication: Results of a randomized, multicenter trial. Arch Intern Med 1999;159(17):2041-50. [Crossref]
• 5. Brown T, Forster RB, Cleanthis M, Mikhailidis DP, Stansby G, Stewart M. Cilostazol for intermittent claudication. Cochrane Database Syst Rev 2021;6(6):CD003748. [Crossref]
• 6. Weintraub WS. The vascular effects of cilostazol. Can J Cardiol 2006;22:56-60. [Crossref]
• 7. Yamada K, Fujimoto Y. Efficacy of cilostazol for intracranial arterial stenosis evaluated by digital subtraction angiography/magnetic resonance angiography. Adv Ther 2011;28(10):866-78. [Crossref]
• 8. Kanlop N, Chattipakorn S, Chattipakorn N. Effects of cilostazol in the heart. J Cardiovasc Med (Hagerstown) 2011;12(2):88-95. [Crossref]
• 9. Barta J, Sanganalmath SK, Kumamoto H, Takeda N, Edes I, Dhalla NS. Antiplatelet agents sarpogrelate and cilostazol affect experimentallyinduced ventricular arrhythmias and mortality. Cardiovasc Toxicol 2008;8(3):127-35. [Crossref]
• 10. Funck-Brentano C, Jaillon P. Rate-corrected QT interval: Techniques and limitations. Am J Cardiol 1993;72(6):17-22. [Crossref]
• 11. Campia U, Gerhard-Herman M, Piazza G, Goldhaber SZ. Peripheral artery disease: Past, present, and future. Am J Med 2019;132(10):1133-41. [Crossref]
• 12. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res 2015;116(9):1509-26. [Crossref]
• 13. Anand SS, Caron F, Eikelboom JW, Bosch J, Dyal L, Aboyans V, et al. Major adverse limb events and mortality in patients with peripheral artery disease: The COMPASS trial. J Am Coll Cardiol 2018;71(20):2306-15. [Crossref]
• 14. Lauters R, Wilkin D. Cilostazol for intermittent claudication caused by peripheral artery disease. Am Fam Physician 2022;105(4):366-7.
• 15. McDermott MM. Exercise training for intermittent claudication. J Vasc Surg 2017;66(5):1612-20. [Crossref]
• 16. Golledge J. Update on the pathophysiology and medical treatment of peripheral artery disease. Nat Rev Cardiol 2022;19(7):456-74. [Crossref]
• 17. Bonaca MP, Hamburg NM, Creager MA. Contemporary medical management of peripheral artery disease. Circ Res 2021;128(12):1868-84. [Crossref]
• 18. Mohammed M, Gosch K, Safley D, Jelani QU, Aronow HD, Mena C, et al. Cilostazol and peripheral artery disease-specific health status in ambulatory patients with symptomatic PAD. Int J Cardiol 2020;316:222-8. [Crossref]
• 19. Endoh M, Yanagisawa T, Taira N, Blinks JR. Effects of new inotropic agents on cyclic nucleotide metabolism and calcium transients in canine ventricular muscle. Circulation 1986;73:117-33.
• 20. Atarashi H, Endoh Y, Saitoh H, Kishida H, Hayakawa H. Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with bradyarrhythmias. J Cardiovasc Pharmacol 1998;31(4):534-9. [Crossref]
• 21. Cohn JN, Goldstein SO, Greenberg BH, Lorell BH, Bourge RC, Jaski BE, et al. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 1998;339(25):1810-6. [Crossref]
• 22. Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991;325(21):1468- 75. [Crossref]
• 23. Wang S, Cone J, Fong M, Yoshitake M, Kambayashi Ji, Liu Y. Interplay between inhibition of adenosine uptake and phosphodiesterase type 3 on cardiac function by cilostazol, an agent to treat intermittent claudication. J Cardiovasc Pharmacol 2001;38(5):775-83. [Crossref]
• 24. Gamssari F, Mahmood H, Ho JS, Villareal RP, Liu B, Rasekh A, et al. Rapid ventricular tachycardias associated with cilostazol use. Tex Heart Inst J 2002;29(2):140-2.
• 25. Sanganalmath SK, Barta J, Takeda N, Kumamoto H, Dhalla NS. Antiplatelet therapy mitigates cardiac remodeling and dysfunction in congestive heart failure due to myocardial infarction. Can J Physiol Pharmacol 2008;86(4):180-9. [Crossref]
• 26. Podzuweit T, Els DJ, McCarthy J. Cyclic AMP mediated arrhythmias induced in the ischaemic pig heart. Basic Res Cardiol 1981;76(4):443-8. [Crossref]
• 27. Wellens HJ, Brugada P, Farre J. Ventricular arrhythmias: Mechanisms and actions of antiarrhythmic drugs. Am Heart J 1984;107:1053-7. [Crossref]
• 28. Day CP, McComb JM, Campbell RW. QT dispersion: An indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990;63(6):342-4. [Crossref]
• 29. Lubinski A, Kornacewicz-Jach Z, Wnuk-Wojnar AM, Adamus J, Kempa M, Królak T, et al. The terminal portion of the T wave: A new electrocardiographic marker of risk of ventricular arrhythmias. Pacing Clin Electrophysiol 2000;23:1957-9. [Crossref]
• 30. Watanabe N, Kobayashi Y, Tanno K, Miyoshi F, Asano T, Kawamura M, et al. Transmural dispersion of repolarization and ventricular tachyarrhythmias. J Electrocardiol 2004;37(3):191-200. [Crossref]
• 31. Cheng JW. Cilostazol. Heart Dis 1999;1(3):182-6. [Crossref]
• 32. Van de Water A, Xhonneux R, Reneman RS, Janssen PA. Cardiac and hemodynamic effects of intravenous R80122, a new phosphodiesterase III inhibitor, in a canine model of myocardial ischemia and heart failure. J Cardiovasc Pharmacol 1992;20(1):18-24. [Crossref]
• 33. Matsui K, Kiyosue T, Wang JC, Dohi K, Arita M. Effects of pimobendan on the L-type Ca2 + current and developed tension in guinea-pig ventricular myocytes and papillary muscle: Comparison with IBMX, milrinone, and cilostazol. Cardiovasc Drugs Ther 1999;13(2):105-13. [Crossref]